A pharmacological approach can be expected to characterize and provide the means of controlling the hypothalamic (VMH and LH) glucoreceptors leading to a better understanding of these central chemoreceptors for the CNS regulation of energy balance and of its abnormal states. This provides the possibility for diagnostic and therapeutic manipulations of a critical link in the integration, whose failure may contribute to such diseases as diabetes mellitus. The necessary correlations require: 1) direct "moment to moment" monitoring of the central processes in the intact animal (unit potentials), 2) neurochemistry of the responding cells, and 3) a means of repeatedly modifying the natural cerebral chemical environment in a graded fashion - initially free of peripheral effects (close-arterial injection). The initial phase will seek to establish the intimate mechanism of the observed hypothalamic glucoreceptor activation and suppression (biphasicity), determining the respective roles of glucose and its breakdown products and the local energy supplied. It is expected to accomplish this by binding studies and by close correlation of function and metabolic patterns and close timing of discrete electrically recorded function with local chemistry along with the use of suitable agonists and antagonists. This will include glucose, glucose analogs, some of which are and some of which are not metabolized, insulin, gold thioglucose, etc. Results with "iontophoretic" application will be compared. Subsequent work will include tailoring and testing of anorexics.